Resveratrol Prevents High Fat/Sucrose Diet-Induced Central Arterial Wall Inflammation and Stiffening in Nonhuman Primates

Abstract

SUMMARY Central arterial wall stiffening driven by a chronic inflammatory milieu accompanies arterial diseases, the leading cause of cardiovascular (CV) morbidity and mortality in Western society. Increase in central arterial wall stiffening, measured as an increase in aortic pulse wave velocity (PWV), is a major risk factor for clinical CV disease events. However, no specific therapies to reduce PWV are presently available. In rhesus monkeys, a two-year diet high in fat and sucrose (HFS) increases not only body weight and cholesterol, but also induces prominent central arterial wall stiffening and increases PWV and inflammation. The observed loss of endothelial cell integrity, lipid and macrophage infiltration, and calcification of the arterial wall were driven by genomic and proteomic signatures of oxidative stress and inflammation. Resveratrol prevented the HFS-induced arterial wall inflammation and the accompanying increase in PWV. Dietary resveratrol may hold promise as a novel therapy to ameliorate increases in PWV.

Metabolic effects of resveratrol: addressing the controversies

“…Resveratrol has also been shown to lower blood pressure in a porcine model of hypertension [155]. Most recently, resveratrol has been shown to reduce the amount of arterial wall inflammation in high fat/high sugar fed rhesus monkeys [156].…”

Resveratrol and its oligomers: modulation of sphingolipid metabolism and signaling in disease

“…Indeed, resveratrol has been shown to be effective in ameliorating hypertension, ischemic heart disease and cardiomyopathy in animal studies (Raj et al 2014). A recent study has shown that resveratrol is effective in reducing arterial wall inflammation and stiffening (hallmarks of vascular aging) in rhesus monkeys fed with highfat diet, possibly through activation of the Nrf2 antioxidant pathway (Mattison et al 2014). Resveratrol also exhibits antioxidant and anti-inflammatory properties due to modulation of other signaling pathways that might impact more significantly on cardioprotection than the modulation of S1P signaling.…”

Synthesis and Evaluation as Prodrugs of Hydrophilic Carbamate Ester Analogues of Resveratrol

“…The last step consisted in the removal of the isopropylidene protecting groups, freeing the hydroxyl functions necessary to enhance the solubility in water of the final products (2)(3)(4)(5)(6) which were finally isolated by preparative reverse-phase HPLC. Purity was in all cases > 95%, as assessed by HPLC-UV analysis.…”

“…The subsequent synthetic steps are equivalent to those reported above for derivatives 7 (2)(3)(4)(5)(6), and consisted in the production of the active urethane (23) followed by transesterification with resveratrol to give a mixture of all the possible mono-, di-and tri-substituted resveratrol derivatives (24)(25)(26)(27)(28). Cleavage of the isopropylidene protecting groups afforded the desired resveratrol-6-deoxygalactosyl carbamate ester conjugates (7)(8)(9)(10)(11), which were isolated by preparative HPLC.…”